A Study of 141W94 Used Alone or in Combination With Zidovudine Plus 3TC in HIV-Infected Patients

Inclusion Criteria

Concurrent Medication:

Allowed:

• Chemoprophylaxis for Pneumocystis carinii pneumonia is required for all patients who have a CD4 cell count <= 200 cells/mm3.
• Topical and/or oral antifungal agents, except for those listed in excluded medications.
• Treatment, maintenance or chemoprophylaxis with approved agents for opportunistic infections as clinically indicated, unless listed in excluded medications.
• All antibiotics as clinically indicated.
• Systemic corticosteroid use for <= 21 days for acute problems is permitted as medically indicated; chronic systemic corticosteroid use is not permitted.
• Recombinant erythropoietin and granulocyte colony-stimulating factor as medically indicated.

Regularly prescribed medications such as:

• antipyretics, analgesics, allergy medications, antidepressants, sleep medications, oral contraceptives (a barrier method is also required for this study), megestrol acetate, testosterone or any other medications, as medically indicated.
• Alternative therapies such as vitamins, acupuncture and visualization techniques are permitted (excluding herbal medications).

NOTE:

• Patients should report the use of these therapies; alternative therapies will be recorded.

Patients must have:

• HIV-1 infection as documented by ELISA and confirmed.
• >= 5,000 HIV-1 RNA copies/ml (within 30 days prior to study entry).
• CD4 cell count >= 50 cells/mm3 within 60 days prior to study entry.
• Signed, informed consent for patients < 18 years of age.

Prior Medication: Required:

• Patients must be on a stable antiretroviral regimen for 30 days prior to study screening and remain on the same regimen until entry.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Any active infection requiring acute treatment within 14 days prior to entry.
• A malignancy that requires systemic therapy other than minimal Kaposi's sarcoma.

NOTE:

• Patients with minimal Kaposi's sarcoma, defined as <= 5 cutaneous lesions and no visceral disease or tumor-associated edema, will be allowed to enroll as long as they do not require systemic therapy for Kaposi's sarcoma.

Patients with the following prior symptoms and conditions are excluded:

• Inability to tolerate ZDV 500-600 mg daily if ZDV was administered previously. Intolerance to ZDV is defined as any grade toxicity that resulted in a dose reduction or termination of ZDV.

Prior Medication:

Excluded:

• Any 3TC therapy prior to entry.
• Any HIV-1 protease inhibitor therapy prior to study entry (e.g., saquinavir, ritonavir, indinavir, nelfinavir, 141W94).
• Any immunomodulator therapy within 30 days prior to entry.
• Active immunization within 30 days prior to entry.

• Any antiretroviral therapy change within 30 days prior to study screening.

  1. Concurrent use of non-protocol specified antiretroviral agents; either investigational or licensed.

• Immunomodulators that affect immunologic or virologic indices such as systemic corticosteroids, thalidomide, or cytokines.
• Concomitant use of rifabutin and/or rifampin.
• Investigational drugs other than 141W94/VX-478.
• Systemic cytotoxic chemotherapy.
• Oral astemizole (Hismanal), carbamazepine (Tegretol), dexamethasone (Decadron), ketoconazole (Nizoral), itraconazole (Sporanox), phenobarbital, phenytoin (Dilantin), terfenadine (Seldane), cisapride (Propulsid), triazolam (Halcion) and midazolam (Versed).
• Herbal medications.